Aldehyde dehydrogenase 2 deficiency promotes skeletal muscle atrophy in aged mice
Aldehyde dehydrogenase 2 deficiency promotes skeletal muscle atrophy in aged mice
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DOI：
10.1152/ajpregu.00304.2021
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发表时间：
2022-06-01
影响因子：
2.8
通讯作者：
Nakazato, Koichi
中科院分区：
文献类型：
--
作者：
Kasai, Akane;Jee, Eunbin;Nakazato, Koichi
乙醛脱氢酶2（ALDH 2）使乙醇产生的乙醛解毒。ALDH 2中的错义单核苷酸多态性（SNP）rs671表现出ALDH 2蛋白的显性阴性形式。在东亚，近40%的人携带不活跃的ALDH 2 *2突变。先前的研究报告ALDH 2 *2与几种疾病的风险增加有关。在这项研究中，我们研究了ALDH 2缺乏对年龄相关性肌肉萎缩的影响及其潜在机制。我们发现，ALDH 2缺乏促进与年龄相关的肌纤维横截面积的损失，特别是在氧化纤维。此外，ALDH 2缺乏加剧了与年龄相关的4-羟基-2-壬烯醛（4-HNE）的积累，这是腓肠肌中氧化应激的标志物。同样，老年ALDH 2基因敲除小鼠的线粒体活性氧（ROS）产生增加，表明ALDH 2缺乏诱导线粒体功能障碍。总之，ALDH 2缺乏促进与年龄相关的肌肉损失，特别是在氧化纤维中，这可能与通过线粒体功能障碍增加的氧化应激积累有关。
Aldehyde dehydrogenase 2 (ALDH2) detoxifies acetaldehyde produced from ethanol. A missense single nucleotide polymorphism (SNP) rs671 in ALDH2 exhibits a dominant-negative form of the ALDH2 protein. Nearly 40% of people in East Asia carry an inactive ALDH2*2 mutation. Previous studies reported that ALDH2*2 is associated with increased risk of several diseases. In this study, we examined the effect of ALDH2 deficiency on age-related muscle atrophy and its underlying mechanisms. We found that ALDH2 deficiency promotes age-related loss of muscle fiber cross-sectional areas, especially in oxidative fibers. Furthermore, ALDH2 deficiency exacerbated age-related accumulation of 4-hydroxy-2-nonenal (4-HNE), a marker of oxidative stress in the gastrocnemius muscle. Similarly, mitochondrial reactive oxygen species (ROS) production increased in aged ALDH2-knockout mice, indicating that ALDH2 deficiency induced mitochondrial dysfunction. In summary, ALDH2 deficiency promotes age-related muscle loss, especially in oxidative fibers, which may be associated with an increased accumulation of oxidative stress via mitochondrial dysfunction.